Introduction And Main Changes - Cardiac & Stroke Networks: Fill & Download for Free

Late graft dysfunction in subjects with kidney transplantation is a major topic of interest, and is due to immunological and non-immunological factors. Increased blood pressure and modified cardiac output is thought to play a role in this process. Here we hypothesize that the relationship between kidney function and cardiac output might be impaired in early stages of kidney allograft dysfunction. To test this hypothesis, we analyzed serial data from 27 transplanted subjects and used these data to derive the relationship between serum creatinine [Cr] and three main parameters connected to the cardiac output that is the heart rate, the systolic blood pressure and the diastolic blood pressure. The main result of the present study is that by focusing on the known relationship between renal function [indexed by creatinine levels] and heart rate or blood pressure, it is possible to show that increases in creatinine levels occur when this relationship is disrupted. In other words, when the changes in creatinine can be explained by heart rate modifications, the system is healthy. Conversely, as soon as the kidney is not responding adequately to a modification in the heart rate, a decrease in kidney function can be observed. These results suggest a new way to look at time-series data in patients underwent kidney transplantation.IntroductionThere is large interest nowadays in the identification of novel biomarkers of late graft dysfunction in subjects with kidney transplantation [1,2].The kidney allograft dysfunction has been shown to be dependent upon many factors, both immunological and non-immunological ones [3]. Among the non-immunological risk factors are blood pressure, diabetes, obesity and cigarette smoke [4]. These factors have been largely studied in relation to cardiovascular diseases. However, it should be noted that the renal allograft itself largely modifies normal blood pressure control through two main mechanisms:[i] the recipient subjects are under lifelong immunosuppressive therapy, which can increase the blood pressure by means of various mechanisms [5] and [ii] the kidney allograft is not innervated [6] and therefore lacks of one of the physiological feedbacks that in normal subjects control its function [7]. The innervation of the kidney, in fact, is known to be important in blood pressure control, and kidney denervation therapies are used in patients who do not respond to drugs [8]. Although it has been reported that the kidney allograft might receive a new innervation, its physiological meaning has been largely questioned [9,10]. It should be noted that it has been reported a relationship between creatinine blood levels [a marker of glomerular filtration rate [GFR] and kidney function] and cardiac output, indexed by the blood pressure [BP] and the heart rate [HR] [11]. The mechanism of such relation is probably due to the strong influence of the heart output on the GFR.In the present paper we hypothesize that the relationship between GFR and cardiac output might be impaired in early stages of kidney allograft dysfunction.To test this hypothesis, we analyzed serial data from a cohort of subjects and used these data to derive the relationship between serum creatinine [Cr] and three main parameters connected to the cardiac output, that is the heart rate, the systolic blood pressure and the diastolic blood pressure. According to our working hypothesis, a kidney with impairment of its function should also show impaired relationship between its GFR [indexed by Cr] and the cardiac output.MethodsThis retrospective observational study evaluated 27 adult patients, who received a deceased kidney transplant more than 5 years before. All the patients received conventional immunosuppression therapy. The main characteristic of the subjects [anthropometric measures, years after transplant, blood chemical data] is reported in Table 1. For their follow-up, subjects have been studied 6 times per year for two years. For the present study, only 10 temporal points per subject have been used [20 months]. Three patients have been excluded from the study because the time series was incomplete. In the present study we further analyzed the creatinine levels, blood pressure and heart frequency collected during the follow-up period.Statistical analysisFor each subject we calculated[i] The change in creatinine level from the beginning to the end of the 20 month follow-up period and[ii] The correlation coefficient between plasma creatinine and blood pressure or heart rate. Finally, the relationship between the change in creatinine and the creatine-BP or Cr-HR correlation was evaluated using correlation analysis [Pearson coefficient] and then linear regression analysis, with a linear model and a quadratic model. The rejection level for statistically significant association was set at p=0.05.ResultsThe relationship between blood pressure and creatinine levels in the same subject over time was very variable among subjects, with some patient exhibiting a strong positive correlation [higher values of creatinine correlated with higher values of blood pressure during the 10 months observational period], absent or even inverse. We then analyze whether this large variability could be linked to the functional status of the kidney and its deterioration over time. Therefore, we analyzed the possible link between a change in creatinine levels over time (indexing the modification of the kidney function) and the correlation of heart function (blood pressure or heart frequency) and the creatinine levels.This correlation analysis did not show any significant relationship between the change in creatinine levels over time and the dependence of creatinine on systolic blood pressure or heart rate [p>0.05]. We therefore conducted a regression analysis using a quadratic model. Also in this case there was no statistical link between the change in creatinine levels and the dependence of creatinine on blood pressure [systolic or diastolic]. However, as shown in Figure 1, there is a non -linear relationship between the change in creatinine level and the heart rate-dependence of creatinine levels [R2=0.37, p=0.008].DiscussionMost of the current literature is focused on the simple relationship between hemodynamic parameters and creatinine or on the trend in creatinine levels or other systemic parameters to explain modifications of creatinine levels in renal allografts.The main result of the present study is that by focusing on the known relationship between renal function [indexed by creatinine levels] and heart rate or blood pressure, it is possible to show that increases in creatinine levels occur when this relationship is disrupted. In other words, when the changes in creatinine can be explained by heart rate modifications, the system is healthy. Conversely, as soon as the kidney is not responding adequately to a modification in the heart rate, a decrease in kidney function can be observed.These results await confirmations from a larger cohort of subjects, but at present they suggest a new way to look at time-series data in patients underwent kidney transplantation.

I’m going to skip characters that have appeared in other, non MCU, Marvel properties. So no Dr. Doom, Magneto, Galactus, Electro, Purifiers etc. Don’t get me wrong, I can’t wait for these characters to appear in the MCU. If I included them though my list would be a whose-who of villains that have already shown up in Sony and Fox movies .-The High EvolutionaryI agree with Mike Schneider here. The High Evolutionary is an interesting character that would be great on the screen. He’s a scientist that is obsessed with evolution and works to perfect his physical form. His experiments are cruel and inhumane and lead to all sorts of hybrid creatures. One of his biggest feats was creating a copy of the Earth. He used this Counter Earth to develop new species and run planet wide experiments. If the experiment was done or didn’t go work the entire population is eradicated. He’s also active on Earth and is a frequent ally of Adam Warlock (despite Adam being a hero). I’ve been wanting to see him in the MCU for a while now. Ever since season 1 of Agents of SHIELD. Before the big Hydra reveal I was convinced the Clairvoyant was the High Evolutionary and when it turned out to be Bill Paxton (who’s fantastic in that role, don’t get me wrong) I was a little disappointed.-Stilt ManSo I go from a master villain to…Stilt Man. Yes, his power is that he has a suit with retractable stilts in the legs. I don’t want him in there as a main villain or even a henchman. Just have him in the opening scene of a Spider-Man movie. Spidey swings along and sees Stilt Man trying to rob a 4th floor appointment. Spider-Man mumbles to himself about people never watching the classics and webs up his legs causing him to fall. Spider-Man goes up to him, webs him up completely and says “I guess you never watched Empire Strikes Back” and swings away.-The Wizard.This long time Fantastic Four villain has fought almost everyone in the comics. He’s a visually interesting character and has enough gadgets in his armor to make Batman’s utility belt jealous. He’s another mad scientist type but is in it for the glory more than the science.-CardiacHe’s more of an anti-hero that ends up fighting the heroes due to his methods. His brother died when a pharmaceutical company withheld medicine that could have saved his life because it wasn’t profitable. He experiments on himself giving him enhanced abilities and the power to channel energy through a specialy made staff. He uses these powers to attack corporations that put profits over the public good. He is not above killing his targets which put’s him in the anti hero category.-EnchantressShe’s an Asgardian sorceress and one of the few main Thor villains that hasn’t shown up. A lot of that is due to her being the typical female villain of the time she was created (desires the hero, uses feminine whiles to cause problems). They can update her so her motivations are political instead of trying to hook up with Thor.-Mole ManAgain agreeing with Mike, Mole Man would be an interesting character. His army of Moloids and Kaiju are more than enough to threaten even the Avengers. He would be a great introduction for the Fantastic Four and would show audiences that the Fantastic Four will not be your standard MCU movie. I imagine him being played by Brendan Gleeson, the actor that played Mad Eye Moody/Barty Crouch in Goblet of Fire. That mix of mania and cruelty would make Mole Man a memorable big screen villain.-ChanceA bounty hunter that does it for the thrill. He’s one dimensional but could be entertaining as a mid tier adversarye. He has a suit that allows him to fly and wrist blasters. Nothing complicated, just a rich adrenaline junkie.-Mister NegativeHis profile is much bigger with the release of the Spider-Man game on PS4 (damn you Sony for getting the licence, I’m just jealous since I have XBOX). He’s another visually interesting character that would be a fantastic main villain. He would work in the movies as well as in the Netflix series. Maybe just change the character from Martin Li to someone else so fans are surprised (like the head of the community center from Iron Fist season 2).-GenoshaNot a single character but a whole nation. They mastered a process that allowed them to create and enslave mutants. They used their mutant slaves for everything from power generation to mining to military support. Give the X-Men a few movies to establish themselves in the MCU and build to a version of X-Tinction agenda where the Genoshans start kidnapping X-Men to enslave and brainwash them.-AnnihlusExtra-dimensional despot that obsessed with destroying all life in our universe? Oh…and is a giant bug? Sign me up! This is a character that could have a slow build up, appearing in a few cosmic MCU series (GOTG, Captain Marvel, Nova etc) and then have a GOTG: Annihilation movie bringing it all together.

It was December 23, at 5:30 am as I heard the phone ring. My father sounded cold and distant as he announced the passing of my mother that morning. He described her short illness over the night as being her usual stomach upset, nothing more than usual. But it had kept her awake all evening and left her out of bed while he had slept during the episode that had taken her life. When he had found her the next morning, she was without a pulse and unresponsive. The decision had been made to not attempt to revive her due to the amount of time between her cardiac arrest and the time she was found.Despite knowing I had seen all the signs of the impending stroke, I was still devastated at the loss of my mother. I had attempted on two or more occasions to tell both my sister and my father after his multiple pulmonary embolism's which had hospitalized him for more than two weeks the prior summer. It had been me, who had stayed with them and assisted them during that time. My sister had visited one of the two weekends, and she had called my mother. But the person who had shown up, spoken with physicians, helped my mother, cleaned house and cooked, noticed my mother’s instances of hoarding, and recognized her lapses of memory were not solely due to stress and lack of sleep. Both my sister and my dad had argued I had exaggerated my mom’s level of cognitive change; yet, my dad would describe times she would call him panicked she had lost the car in a parking lot and couldn’t find it to drive home. The two arguments didn't combine well. Mom had been showing signs of trans ischemic attacks (TIAs) for a long time prior to her death, but no one was fully acknowledging them due to not talking about her behaviors.The timing and circumstances surrounding her death created problems for my going home. My parents lived four hours away from myself and my ex; whom I share custody of our seven younger children at the time. For that period of the holidays, my parenting time ended on Christmas day at 3:30 pm. His mother lives five miles away from my parents, but my ex had no intention of visiting his mother that year. We share no loss of love between us at this time, as my ex is a diagnosed narcissist who seeks to punish me at every turn for leaving him. Once he heard my mom had died, it was game on. My older four children sought to soften him some during the ordeal.My love and I both either were paid on December 24th or were waiting on checks from subcontracting work promised 2–4 days prior and as usual, was late. Anyone who works a subcontracting position understands that a company paying on time is a rarity and a contract that you will discount in order to keep. Most contracts hold onto their money, pay contractors last, and squeeze work from them months ahead of paying them. This caused us to be months behind in Christmas shopping and we had promised to assist a friend in buying groceries for her family to tide them over until her child support would arrive after the first of the year. We couldn't up and leave town without feeding them.Upon my arrival, rather than call me, my sister and my dad had gone to the funeral home without me. Despite having told me they would wait until I arrived and everything would occur after the holiday. My mother was to be created. There would be no viewing in a casket; only the disposition of ashes in a gravesite at the veterans’ memorial cemetery. It bothered me to be excluded, but I chalked it up to my father's desire to get things done and over.During the following days, it became clear my younger sister and her eldest daughter were now the financial surrogates for my father. I was kept at arm’s length. Any questions I asked were answered with one and two-word answers telling me my sister and her daughter were in charge of dad and his money. My sister stated dad was all but incompetent.She had two children who had known and identified drug problems. One with a police record for drugs. Her ex-husband had been an abusive alcoholic from their first year of marriage. Knowing this, she had quickly gathered my mom’s medications to take for disposal. I have fibromyalgia and had missed my most recent appointment for my medications. I rarely if ever took my pain meds according to orders, instead, I would wait until I couldn't stand the pain and then begin my medicine. This meant I never used all of my scripts and was technically non-compliant in the best way because I avoided using too much medication. But it also meant I would often be without pain meds on hand when I needed them. Fibromyalgia flares with cold and stress; something the week was none short of, combined with the fact my niece and her fiance had taken the only other decent bed in the house and we were left to sleep on the drafty floor on a leaking air mattress meant I was in a full-blown exacerbation in days. When this happened, I realized I had four pain meds of my own. My mom had knee surgery in the last year and been prescribed the same meds. She had taken one and gotten ill, and taken no more.I opened the bag and took out mom’s pills. Closed up the bag. I then called my sister into the room and explained my doctor was on vacation as of December 22, the order had to be handwritten, delivered in person to be filled. I had let two such orders expire but the funeral, sleeping on the floor, the extreme cold, the stress, and my ex demanding the children be driven back to him and possibly miss the funeral were exacerbating my disease process.She quickly called me a drug addict! She accused me of having taken one of the pills prior to my discussion with her. I hadn't done that. She told my fibromyalgia was an imaginary disease and my doctor was a pill-pushing quack. All this from an unlicensed LPN who hadn't practiced in more than 10 years and wasn't keeping up with her continuing education hours. My fiance and she began to argue over it, and she attempted to tell him he knew nothing about it, claiming I was hyped up and glassy-eyed as I was nervously telling my story about no more scripts at home when she knew that was just a cover story I made up. She then proceeded to run to my dad and announce to him I was a bonafide drug addict the next morning!! Soewing her lies about how I had taken the medication. But upon hearing her attack on my character, I promptly returned the medication where I found it. I had not taken one pill. The bottle was intact. Her story was nothing more than her fabrication and conjecture.I approached my dad regarding the lie and his comment was he didn't like me taking those medicines. I told him neither did I, but there were times everyone needed to take them for pain. I just experienced that level of pain more frequently. We discussed how often I saw my physician and how often I got refills. I also pointed out that I was well aware of how easily our family could become addicted. Which was why I was so non-compliant with my meds. But it was clear my sister had damaged my relationship with my dad.We had a memorial service for our mother and both of us were to speak. I was unaware that I was the introduction to my sister who was to be the main act. I had taken my part very seriously as I had reflected over my mom’s life and realized that the people who would be arriving to remember her would be from very separate groups and not many overlapping. My entire memorial was about how my mom volunteered or worked in those groups and how her work in those groups brought those people to that moment. My speech took too long my dad told me when I was done. I broke down in tears. Apparently, he had only allowed me to speak because he felt he had to let me do something.My sister gave her somewhat comedic speech and the children lead by the oldest two grandchildren sang their grannie’s favorite songs.The peace ended there. Early Friday morning my sister and father went to change the will and enter her as his monetary POA. I was left out and told nothing. Not an hour after they arrived I was told that she was given all rights to his medical and personal powers of attorney and would be the executor of his will. I was stunned. It seems her little scheme of playing me up as the drug addict older sister had worked!